Neeraj J. Gandhi

Motor Functions of the Superior Colliculus

The mammalian superior colliculus (SC) and its nonmammalian homolog, the optic tectum, constitute a major node in processing sensory information, incorporating cognitive factors, and issuing motor commands. The resulting action-to orient toward or away from a stimulus-can be accomplished as an integrated movement across oculomotor, cephalomotor, and skeletomotor effectors. The SC also participates in preserving fixation during intersaccadic intervals. This review highlights the repertoire of movements attributed to SC function and analyzes the significance of results obtained from causality-based experiments (microstimulation and inactivation). The mechanisms potentially used to decode the population activity in the SC into an appropriate movement command are also discussed.

Endpoint accuracy in saccades interrupted by stimulation in the omnipause region in monkey

Electrical stimulation of the omnipause neuron region (OPN) at saccade onset results in interrupted saccades (IS)- eye movements which pause in midflight, resume after a brief period, and end near the target location. Details on the endpoint accuracy of IS do not exist, except for a brief report by Becker et al. (1981). Their analysis emphasized the accuracy of IS relative to the visual target which remained on during the interrupted period. We instead quantified the metric properties of IS relative to nonstimulated saccades during a target flash paradigm. Our results show that IS tend to be slightly hypermetric relative to the nonstimulated saccades to the same target location. The amount of overshoot is not correlated with target eccentricity. Detailed analyses also indicate that the standard deviations of the endpoint in IS are not significantly larger than those for nonstimulated saccades, although there was a much larger variability produced in eye position during the interruption. Both these latter observations support the notion that saccades are controlled by an internal negative feedback system. Also, the size of the remaining motor error during the interrupted period is one factor influencing when an IS resumes, but the variability in this measure is large particularly for smaller motor errors. Recent results have suggested that the resettable neural integrator involved in the feedback loop may be reset after each saccade through an exponential decay process. To probe the properties of the neural integrator, we varied the duration of interruption between the initial and resumed saccades and sought a systematic overshoot in the final eye position with increasing interruption period and variable initial saccade size. Our results showed the neural integrator does not decay during the pause period of interrupted saccades.

Cortical and subcortical contributions to coordinated eye and head movements.

This paper summarizes recent experiments conducted by the authors - experiments that studied the behavioral characteristics of large gaze shifts and the neural bases of coordinated movements of the eyes and head.

Studies of the Role of the Paramedian Pontine Reticular Formation in the Control of Head‐Restrained and Head‐Unrestrained Gaze Shifts

Abstract: Results of three experiments related to the role of the paramedian pontine reticular formation (PPRF) in the control of gaze are described. (1) Chronic unit recording methods, used to study the on‐directions of short‐lead burst neurons in head‐restrained monkeys, and (2) reversible inactivation techniques confirmed the traditional view of the importance of PPRF in the control of horizontal eye movements. Reversible inactivation of neurons in the vicinity of identified short‐lead burst neurons produced dramatic reductions in the speed of saccades to horizontal target displacements. The reductions in velocity were largely compensated for by an increase in saccade duration. Only minor, if any, effects were observed upon the velocity, duration, and amplitude of saccades to upward target displacements. (3) Microstimulation was applied to omnipause neurons to gate activity of excitatory burst neurons that discharge during coordinated eye‐head movements. The microstimulation failed to noticeably slow (prevent) head movements when stimulation was applied during (prior to onset of) gaze shifts, suggesting that signals relayed to motoneurons innervating the neck muscles are not inhibited by the omnipause neurons. In other words, the desired gaze signal is parsed into eye and head pathways upstream of the excitatory burst neurons.

Experimental control of eye and head positions prior to head-unrestrained gaze shifts in monkey

A coordinated movement of the eyes and head in the head-unrestrained condition is often used to change orientation between targets. Under natural conditions, these gaze shifts are typically generated with the eyes roughly centered in the orbits. To achieve experimental control of eye and head positions, a miniature laser was mounted on the head implants of monkeys that were trained to point the head to one target and direct gaze to another before generating a head-unrestrained gaze shift to a third target (dissociation paradigm). For comparison, monkeys were also required to make gaze shifts between stimuli, without any constraints on eye and head positions (standard paradigm). Analyses indicated that movement parameters, limited to horizontal gaze shifts, were similar for both behavioral conditions. Thus, the proposed technique and behavioral paradigm, when used in conjunction with electrophysiological and pharmacological experiments, may facilitate the study of neural control of gaze.

Real-time data acquisition and control system for the measurement of motor and neural data.

This paper outlines a powerful, yet flexible real-time data acquisition and control system for use in the triggering and measurement of both analog and digital events. Built using the LabVIEW development architecture (version 7.1) and freely available, this system provides precisely timed auditory and visual stimuli to a subject while recording analog data and timestamps of neural activity retrieved from a window discriminator. The system utilizes the most recent real-time (RT) technology in order to provide not only a guaranteed data acquisition rate of 1 kHz, but a much more difficult to achieve guaranteed system response time of 1 ms. The system interface is windows-based and easy to use, providing a host of configurable options for end-user customization.

Responses of neurons in the rostral ventrolateral medulla to whole body rotations: comparisons in decerebrate and conscious cats

The responses to vestibular stimulation of brain stem neurons that regulate sympathetic outflow and blood flow have been studied extensively in decerebrate preparations, but not in conscious animals. In the present study, we compared the responses of neurons in the rostral ventrolateral medulla (RVLM), a principal region of the brain stem involved in the regulation of blood pressure, to whole body rotations of conscious and decerebrate cats. In both preparations, RVLM neurons exhibited similar levels of spontaneous activity (median of ∼17 spikes/s). The firing of about half of the RVLM neurons recorded in decerebrate cats was modulated by rotations; these cells were activated by vertical tilts in a variety of directions, with response characteristics suggesting that their labyrinthine inputs originated in otolith organs. The activity of over one-third of RVLM neurons in decerebrate animals was altered by stimulation of baroreceptors; RVLM units with and without baroreceptor signals had similar responses to rotations. In contrast, only 6% of RVLM neurons studied in conscious cats exhibited cardiac-related activity, and the firing of just 1% of the cells was modulated by rotations. These data suggest that the brain stem circuitry mediating vestibulosympathetic reflexes is highly sensitive to changes in body position in space but that the responses to vestibular stimuli of neurons in the pathway are suppressed by higher brain centers in conscious animals. The findings also raise the possibility that autonomic responses to a variety of inputs, including those from the inner ear, could be gated according to behavioral context and attenuated when they are not necessary.

Single cell signals: an oculomotor perspective

We examine the activity of individual neurons in three different brain areas where firing rate, number of spikes (the integral of discharge rate), and the location of the active cell within a motor map are used as coding schemes. The correlations between single cell activity and the parameters of a movement range from extremely tight (motoneurons) to non-existent (superior colliculus). We argue that the relationship between the activity of single cell activity and global aspects of behavior are best described as coarse coding for all three types of neuron. We also present evidence, in some cases in a preliminary and suggestive form, that the distribution of spikes in time, rather than average firing rate, may be important for all three neuron types, including those using a place code. Finally, we describe difficulties encountered in obtaining an estimate of the motor command when more than one oculomotor system is active.

Coordination of eye and head components of movements evoked by stimulation of the paramedian pontine reticular formation

Constant frequency microstimulation of the paramedian pontine reticular formation (PPRF) in head-restrained monkeys evokes a constant velocity eye movement. Since the PPRF receives significant projections from structures that control coordinated eye-head movements, we asked whether stimulation of the pontine reticular formation in the head-unrestrained animal generates a combined eye-head movement or only an eye movement. Microstimulation of most sites yielded a constant-velocity gaze shift executed as a coordinated eye-head movement, although eye-only movements were evoked from some sites. The eye and head contributions to the stimulation-evoked movements varied across stimulation sites and were drastically different from the lawful relationship observed for visually-guided gaze shifts. These results indicate that the microstimulation activated elements that issued movement commands to the extraocular and, for most sites, neck motoneurons. In addition, the stimulation-evoked changes in gaze were similar in the head-restrained and head-unrestrained conditions despite the assortment of eye and head contributions, suggesting that the vestibulo-ocular reflex (VOR) gain must be near unity during the coordinated eye-head movements evoked by stimulation of the PPRF. These findings contrast the attenuation of VOR gain associated with visually-guided gaze shifts and suggest that the vestibulo-ocular pathway processes volitional and PPRF stimulation-evoked gaze shifts differently.

Open-loop simulations of the primate saccadic system using burst cell discharge from the superior colliculus

Saccade-related burst neurons (SRBNs) in the monkey superior colliculus (SC) have been hypothesized to provide the brainstem saccadic burst generator with the dynamic error signal and the movement initiating trigger signal. To test this claim, we performed two sets of open-loop simulations on a burst generator model with the local feedback disconnected using experimentally obtained SRBN activity as both the driving and trigger signal inputs to the model. First, using neural data obtained from cells located near the middle of the rostral to caudal extent of the SC, the internal parameters of the model were optimized by means of a stochastic hillclimbing algorithm to produce an intermediate-sized saccade. The parameter values obtained from the optimization were then fixed and additional simulations were done using the experimental data from rostral collicular neurons (small saccades) and from more caudal neurons (large saccades); the model generated realistic saccades, matching both position and velocity profiles of real saccades to the centers of the movement fields of all these cells. Second, the model was driven by SRBN activity affiliated with interrupted saccades, the resumed eye movements observed following electrical stimulation of the omnipause region. Once again, the model produced eye movements that closely resembled the interrupted saccades produced by such simulations, but minor readjustment of parameters reflecting the weight of the projection of the trigger signal was required. Our study demonstrates that a model of the burst generator produces reasonably realistic saccades when driven with actual samples of SRBN discharges.